In the context of gene regulation:transactivation is the increased rate ofgene expression triggered either by biological processes or by artificial means, through the expression of an intermediate transactivator protein.
In the context of receptor signaling,transactivation occurs when one or more receptors activate yet another;[1][2] receptor transactivation may result from thecrosstalk ofsignaling cascades or the activation ofG protein–coupled receptor hetero-oligomer subunits, among other mechanisms.[1]
Transactivation can be triggered either by endogenous cellular or viral proteins, also calledtransactivators. These protein factorsact in trans (i.e.,intermolecularly).HIV andHTLV are just two of the many viruses that encode transactivators to enhance viral gene expression. These transactivators can also be linked to cancer if they start interacting with, and increasing expression of, a cellularproto-oncogene. HTLV, for instance, has been associated with causingleukemia primarily through this process. Its transactivator,Tax, can interact withp40, inducing overexpression ofinterleukin 2,interleukin receptors,GM-CSF and thetranscription factorc-Fos. HTLV infectsT-cells and via the increased expression of these stimulatorycytokines andtranscription factors, leads to uncontrolled proliferation of T-cells and hencelymphoma.
Artificial transactivation of a gene is achieved by inserting it into the genome at the appropriate area as transactivator gene adjoined to special promoter regions ofDNA. The transactivator geneexpresses a transcription factor that binds to specific promoter region of DNA. By binding to thepromoter region of a gene, the transcription factor causes that gene to be expressed. The expression of one transactivator gene can activate multiple genes, as long as they have the same, specific promoter region attached. Because the expression of the transactivator gene can be controlled, transactivation can be used to turn genes on and off. If this specific promoter region is also attached to areporter gene, we can measure when the transactivator is being expressed.
For instance, there are indications that both D1 and D2 receptors can trans-activate the brain-derived neurotrophic factor (BDNF) receptor in neurons (Swift et al., 2011). These two dopamine receptors can also regulate calcium channels through a direct protein–protein interaction in vivo (Kisilevsky and Zamponi, 2008; Kisilevsky et al., 2008). Direct interaction of D1 and D2 receptors and Na+-K+-ATPase has also been demonstrated (Hazelwood et al., 2008; Blom et al., 2012).